Evaluation of tumor budding, desmoplastic reaction, and lymphocytic infiltration in predicting survival for pancreatic ductal adenocarcinoma

Anıl Alpsoy; Aysen Yavuz; Kubra Simsek; Busra Altunay; Mustafa Karaca; Betul Unal; Cumhur I Bassorgun; Ali M Tatli; Gulsum O Elpek

doi:10.4251/wjgo.v17.i6.107021

Evaluation of tumor budding, desmoplastic reaction, and lymphocytic infiltration in predicting survival for pancreatic ductal adenocarcinoma

World J Gastrointest Oncol. 2025 Jun 15;17(6):107021. doi: 10.4251/wjgo.v17.i6.107021.

Authors

Anıl Alpsoy¹, Aysen Yavuz², Kubra Simsek², Busra Altunay³, Mustafa Karaca⁴, Betul Unal⁵, Cumhur I Bassorgun², Ali M Tatli⁶, Gulsum O Elpek⁷

Affiliations

¹ Afyonkarahisar State Hospital, Afyonkarahisar 03000, Türkiye.
² Department of Pathology, Akdeniz University, School of Medicine, Antalya 07070, Türkiye.
³ Kütahya City Hospital, Kütahya 43000, Türkiye.
⁴ Department of Internal Medicine, Akdeniz University, Antalya 07070, Türkiye.
⁵ Antalya Bilim University, Antalya 07070, Türkiye.
⁶ Department of Oncology, Akdeniz University, School of Medicine, Antalya 07070, Türkiye.
⁷ Department of Pathology, Akdeniz University, School of Medicine, Antalya 07070, Türkiye. elpek@akdeniz.edu.tr.

Abstract

Background: Although previous findings indicated that pathological assessment of tumor budding (TB), desmoplastic reaction (DR), and tumor-infiltrating lymphocytes (TILs) may play a role in determining tumor behavior in many malignancies, the relationship between TB, DR, and TILs in patients with pancreatic ductal adenocarcinoma (PDAC) is still unknown.

Aim: To evaluate relationships of TB, DR, and TILs with histopathological parameters and determine their prognostic value in patients with PDAC.

Methods: The study cohort comprised 100 patients diagnosed with PDAC. Peritumoral budding (PTB) and intratumoral budding (ITB) were assessed according to the International Tumor Budding Consensus Conference guidelines. DR was classified based on stromal maturation. TILs were evaluated semiquantitatively with a 5% cutoff. Additionally, cases were categorized into two groups according to lymphocyte density: No/Low lymphocytes and medium/high lymphocytes.

Results: A significant correlation was observed between ITB and PTB (r = 0.890). Higher PTB was associated with fewer TILs and immature stroma (P < 0.001). PTB and TILs were significantly related to tumor dimension, lymphovascular invasion, lymph node metastasis (LNM), and stage (P < 0.005). ITB was also associated with the presence of lymph node involvement. The results of the univariate analysis revealed a significant correlation between poor survival rates and the presence of lymphovascular invasion, LNM, PTB, ITB, and TILs according to scoring (P < 0.001). The multivariate analysis revealed LNM, PTB, ITB, and TILs according to scoring as independent prognostic factors.

Conclusion: TB assessment stratified patients with PDAC. PTB-ITB correlation showed diagnostic relevance of ITB in biopsy specimens. The prognostic significance of DR and interplay with TIL subsets warrant further investigation.

Keywords: Desmoplastic reaction; Pancreatic ductal adenocarcinoma; Prognostic factors; Tumor budding; Tumor microenvironment; Tumor-infiltrating lymphocytes.